System Architecutre

     POINeT integrates PPI information collected by various protein databases, and provides PPI filtering and network topology analysis capability. PPI filtering mainly focuses to filter PPIs with biological significance and of relative importance, and the capability of analyzing network topologies, including measurements such as Closeness Centrality, Degree Centrality, Eccentricity, Radiality, and Centroids. Using the topological features in biological networks, nodes playing different roles can be selected and ranked. Novel targets with biological significances can also be evaluated. Besides the PPI information, several sets of tissue-specific expression profiles are also available online. The query results of POINeT can be downloaded in multiple formats, including Excel, sif (simple interaction format), and txt formats, and POINeT provides a straightforward viewer with sufficient functionalities. No additional software installations are required. Figure 1 illustrates the overall system architecture of POINeT. Through the integration of data from various sources, POINeT provides PPI network related services in one query.

Figure 1 - The overall system architecture of POINeT. The system architecture of POINeT, through the integration of data from various sources, POINeT is able to provide efficient PPI network related services in one query.

   The flow chart of filtering Query-Query, GO, and Interologs PPIs, and downloadable items are depicted in Figure 2. Briefly, user inputs the query terms (genes or proteins), which will be recorded as attr-Query, into POINeT to search for all available PPIs, referred as ppi-AllPPI. If a query has no available PPI, POINeT stores it as attr-noInteractionQuery. If certain filtering criteria were set in the query page, such as 'Number of iterations' or 'Number of literatures', the number of PPIs included in ppi-AllPPI will change accordingly. Subsequently, nodes involved in ppi-AllPPI will be in attr-Interactor table and the degrees of these nodes will be calculated. Nodes with degree >= 2 are defined as mediators and recorded in attr-Mediator table. Also, nodes with degrees >= 2 will form another network, which removes all nodes with degree = 1 and is denoted as ppi-Degree2. This network can reduce the complexity of network visualization and illustrate how queries are connected through these hubs. These hubs may play the role of regulators in this network. If a query node interacts with itself and forms homodimer, this node will be recorded in attr-HomoDimer table. Furthermore, if two interactors of one interaction were both present in attr-Query table, this interaction will be documented in ppi-QQPPI. Interactors in ppi-QQPPI network will be recorded in attr-QQ table. Interologs in different species can be inferred systematically using NCBI HomoloGene database. These interologs PPI will be recorded in ppi-InterologsPPI table. Using gene2go mapping table provided by NCBI, whether two interactors of one PPI sharing the same GO annotation will be noted, resulting in ppi-GOPPI network. Finally, if interactors of ppi-QQPPI are present in attr-Mediator table, these interactors will be placed in attr-QH table, which denotes that a node exhibits both query and hub in the network. POINeT will merge ppi-QQPPI, ppi-GOPPI, and ppi-InterologsPPI into ppi-FilteredPPI. This network contains PPIs with relative reliable and certain biological significances. This network, which is smaller than ppi-AllPPI, can be visualized and analyzed with ease and extended with other selected features. The above described tables can be downloaded in multiple formats.

Figure 2 - The analysis results and downloadable items provided by POINeT.